JACC: HEART FAILURE VOL. 6, NO.

1, 2018

ª 2018 THE AUTHORS. PUBLISHED BY ELSEVIER ON BEHALF OF THE AMERICAN ISSN 2213-1779

COLLEGE OF CARDIOLOGY FOUNDATION. THIS IS AN OPEN ACCESS ARTICLE UNDER https://doi.org/10.1016/j.jchf.2017.10.001

THE CC BY-NC-ND LICENSE (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Efficacy of Intravenous Furosemide

Versus a Novel, pH-Neutral Furosemide
Formulation Administered
Subcutaneously in Outpatients With
Worsening Heart Failure
Nisha A. Gilotra, MD,a Oluseyi Princewill, MD,b Bonnie Marino, RN,a Ike S. Okwuosa, MD,a Jessica Chasler, PHARMD,a
Johana Almansa, DNP,a Abby Cummings, CRNP,a Parker Rhodes, MS,a Julianne Chambers, RN,a
Kimberly Cuomo, CRNP,a Stuart D. Russell, MDa

ABSTRACT

OBJECTIVES This study sought to determine the efficacy and safety of a novel, pH-neutral formulation of furosemide
administered subcutaneously (SC) for treatment of acute decompensated heart failure (HF).

BACKGROUND Congestion requiring intravenous (IV) administration of a diuretic agent is the main reason patients
with HF present for acute medical care.

METHODS Outpatients presenting with decompensated HF were randomized to receive a single SC or IV dose of
furosemide. Primary outcome was 6-h urine output, and secondary outcomes were weight change, natriuresis, and
adverse events.

RESULTS Forty-one patients were randomized: 19 were treated with IV (mean dose: 123
47 mg) and 21 with SC furosemide
(fixed dose of 80 mg over 5 h). The 6-h urine output in the IV group was not significantly different from that in the SC
furosemide group (median IV: 1,425 ml; interquartile range [IQR]: 1,075 to 1,950 ml; vs. median SC: 1,350 ml; IQR: 900 to
1,900 ml; p ¼ 0.84). Additionally, mean weight loss was not significantly different (1.5
1.1 kg in the IV group vs. 1.5
1.2
kg in the SC group; p ¼ 0.95). Hourly urine output was significantly higher in the IV group at hour 2 (425 ml in the IV group vs.
250 ml in the SC group; p ¼ 0.02) and higher in the SC group at hour 6 (125 ml, IV group vs. 325 ml, SC group; p ¼ 0.005).
Natriuresis was higher in the SC group (IV: 7.3
35.3 mEq/l vs. SC: 32.8
43.6 mEq/l; p ¼ 0.05). There was no worsening renal
function, ototoxicity, or skin irritation with either formulation. Thirty-day hospitalization rates were similar.

CONCLUSIONS In this phase II trial, we did not identify significant differences between urine output obtained with
pH-neutral furosemide administered SC and that obtained by IV. This method of decongestion may allow treatment
at home and reduced HF resources and warrants further investigation. (Sub-Q Versus IV Furosemide in Acute Heart
Failure; NCT02579057) (J Am Coll Cardiol HF 2018;6:65–70) © 2018 The Authors. Published by Elsevier on behalf
of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).

T he heart failure (HF) syndrome is character-

ized in many patients by a vicious cycle of
recurrent congestion (1). This syndrome
results in high use of health care resources, with
more than 1 million hospitalizations for HF annually
and a 25% 30-day readmission rate (2). Diuretic
agents remain the mainstay treatment of both chronic
and acute decompensated heart failure (ADHF) (3).

a
From the Division of Cardiology, Department of Medicine, Johns Hopkins Hospital, Baltimore, Maryland; and the
b
MedStar Cardiology Associates, MedStar Heart and Vascular Institute, Olney, Maryland. This investigation was supported by
scPharmaceuticals. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Manuscript received July 19, 2017; revised manuscript received October 3, 2017, accepted October 4, 2017.
66 Gilotra et al.
Subcutaneous Furosemide in Heart Failure
ABBREVIATIONS The loop diuretic furosemide was first intro-
AND ACRONYMS duced more than 50 years ago. In its oral
formulation, furosemide has a peak onset of
ADHF = acute decompensated
heart failure
action within 1 to 2 h, which then wanes;
however, particularly in the setting of wors-
HF = heart failure
ening edema of the gut, oral absorption can
IV = intravenous
be quite erratic (4). Therefore, in these situa-
NYHA = New York Heart
Association
tions, patients may require intravenous (IV)
diuretic therapy, often resulting in HF hospi-
SC = subcutaneous
talization. In fact, nearly 90% of patients
with ADHF are treated with IV loop diuretics (5).
With the rising cost of HF hospitalization (6), novel
strategies are being used worldwide to keep HF pa-
tients out of the hospital. In 2012, we established
the Johns Hopkins Heart Failure Bridge Clinic
(HFBC), an outpatient HF disease management pro-
gram with the ability to administer IV diuretics. In
2016, we administered IV furosemide 441 times.
Other studies have shown that such a strategy is
safe and results in significant urine output (7). How-
ever, this therapy still requires a clinic visit, use of re-
sources, patient inconvenience, and peripheral IV
catheter placement.
SEE PAGE 71
Furosemide for injection (or furosemide USP) has an
alkaline pH ranging from 8.0 to 9.3, thus limiting the
ability to administer the drug subcutaneously (SC) due
to discomfort upon injection and local skin irritation
(8). A novel, buffered, pH-neutral formulation of
furosemide was developed for SC administration
(scFurosemide, product SCP-101, scPharmaceuticals,
Lexington, Massachusetts) with the aim of developing
an alternative to IV furosemide that could ultimately
be used by patients outside the acute care setting.
scFurosemide injection (80 mg/0 ml) is administered
by SC infusion, with 30 mg delivered in the first hour
and 12.5 mg/h delivered for the subsequent 4 h for a
total dose of 80 mg. The SC infusion has been
demonstrated to be well tolerated and can achieve
therapeutic drug levels in stable chronic HF subjects
(9). We sought to study the efficacy and safety of
scFurosemide administered SC in patients with wors-
ening HF requiring IV diuresis in the outpatient clinic.
METHODS
STUDY DESIGN. This was a randomized proof-of-
concept pilot study.
STUDY PARTICIPANTS. Adult outpatients who pre-
sented to the HFBC with a history of HF treatment of
least 3 months or HF hospitalization within 60 days
and who were identified by providers as requiring IV
diuresis for worsening HF were eligible for the study.
JACC: HEART FAILURE VOL. 6, NO. 1, 2018
JANUARY 2018:65–70
Patients were categorized as New York Heart Associ-
ation functional classes II to IV with signs and/or
symptoms of volume overload. Exclusion criteria
were as follows: patients presenting with signs or
symptoms where chance of hospitalization was
high, such as myocardial ischemia, uncontrolled
arrhythmia, infection, fever >101 F (38 C), hemody-
namic instability (systolic blood pressure #80 mm Hg,
symptomatic hypotension, diastolic blood pressure
$120 mm Hg, or evidence of hypertensive urgency or
emergency), respiratory compromise, mental status
changes, acute kidney injury defined as >25% increase
in serum creatinine from baseline, hypokalemia
defined as serum potassium <4.0 mmol/l, patients
receiving experimental medication therapy or
currently participating in another cardiovascular
research study, presence of or need for urinary bladder
catheterization, urinary tract abnormality or disorder
interfering with urination, or allergy to loop diuretics.
Subjects were enrolled from February 2016 to April
2017, and all participants provided written informed
consent. Patients could only be enrolled in the study
once during the study period. The study was approved
by the Johns Hopkins Institutional Review Board.
RANDOMIZATION AND TREATMENT ADMINISTRATION.
Subjects were randomly assigned, in a 1:1 ratio, to
receive a single dose of IV furosemide or scFur-
osemide. Randomization was performed using block-
stratified assignments by using a computerized
pseudorandom number generator by the Johns Hop-
kins Hospital Investigational Drug Service, which
dispensed the study drug and was blinded to clinical
outcomes. All subjects underwent examinations for
baseline vital signs, weight, and laboratory testing
(including serum sodium, potassium, creatinine, pro–
B-type natriuretic peptide [proBNP] and urinary so-
dium concentrations). All laboratory testing occurred
at the Johns Hopkins core laboratory. Subjects ran-
domized to IV therapy underwent usual care, with
placement of peripheral IV catheter and administra-
tion of diuretic agent as an IV bolus. Dose was
calculated based on the subject’s outpatient oral
dose, typically with a 1:1 conversion, with a maximum
IV dose of 160 mg. The SC group received 80 mg of
scFurosemide administered over 5 h (30 mg in the
first hour, followed by 12.5 mg/h for 4 h) by using an
infusion pump system (Perfusor space infusion
pump, B. Braun Medical, Bethlehem, Pennsylvania)
and a standard commercial infusion set. Subjects also
received potassium or magnesium supplementation
according to standard of care protocol in the diuresis
clinic. Subjects vital signs (blood pressure and heart
rate) and urine output were monitored for 6 h. Sub-
jects urinated in a pre-specified container with
JACC: HEART FAILURE VOL. 6, NO. 1, 2018 Gilotra et al. 67
JANUARY 2018:65–70 Subcutaneous Furosemide in Heart Failure

marked milliliter measurements, either at bedside or

T A B L E 1 Baseline Characteristics and Pre-Diuresis Assessment
in a restroom facility located in the clinic room itself.
Urine output was measured and recorded by a clinic IV SQ Total
(n ¼ 19) (n ¼ 21) (N ¼ 40)
staff member on an hourly basis over the 6-h study
Age, yrs 54
13 59
13 57
13
observation period. During diuretic administration,
Females 9 (47) 13 (62) 22 (55)
all patients underwent a 100-ml fluid consumption Race
restriction. At 6 h, patients’ weight measurements White 5 (26) 8 (38) 13 (33)
and laboratory testing were repeated. They were Black 14 (74) 12 (57) 26 (65)
monitored for side effects and adverse events, Asian 0 (0) 1 (5) 1 (2.5)

including access site discomfort (burning, itching, Body mass index, kg/m2 39.7
11.2 37.8
11.3 38.7
11.2
Comorbidities (%)
pain, and rash), ototoxicity, change in renal function
Atrial fibrillation 6 (32) 7 (33) 13 (33)
and potassium concentrations, and symptoms of po-
Coronary artery disease 8 (42) 6 (29) 14 (35)
sitional lightheadedness. Subjects were then dis- Diabetes mellitus 12 (63) 7 (33) 19 (48)
charged from the clinic, and were followed for clinical Chronic kidney disease 9 (47) 11 (52) 20 (50)
events for 30 days. Chronic obstructive pulmonary 4 (21) 4 (19) 8 (20)
disease
ENDPOINTS. The primary outcome was volume of
Hypertension 12 (63) 18 (86) 30 (75)
urine output at 6 h. Secondary outcomes included
Left ventricular ejection fraction, % 20 (20–55) 25 (15–55) 25 (15–55)
weight change, hourly urine output, natriuresis, fre- Heart failure with preserved 5 (26) 8 (38) 13 (33)
quency of adverse events, and 30-day hospitalization ejection fraction

rate. A follow-up telephone call and medical chart Amyloid 2 (11) 0 (0) 2 (5)
Furosemide daily dose, mg 228
174 261
164 246
167
review were performed at 1, 7, and 30 days to assess
Beta-blocker 15 (79) 16 (76) 31 (78)
for side effects, further IV diuretic needs, and
ACE-inhibitor/ARB 10 (53) 13 (62) 23 (58)
hospitalization.
Aldosterone antagonist 7 (37) 8 (38) 15 (38)
SAMPLE SIZE. Based on experience in the clinic, we New York Heart Association functional class
estimated the 6-h urine output to be approximately II 7 (37) 5 (24) 12 (30)
1,200 ml in the IV group. We considered a difference III 11 (58) 13 (62) 24 (60)

in urine output of 500 ml to be clinically significant. IV 1 (5) 3 (14) 4 (10)

Systolic blood pressure, mm Hg 118
21 124
26 121
24
Using a SD of 500 ml, we estimated we would need
Diastolic blood pressure, mm Hg 68
13 72
14 70
14
approximately 20 patients in each group to have 80%
Heart rate, beats/min 86
16 83
16 85
16
power to detect a clinically significant difference in
S3 heart sound 2 (11) 0 (0) 2 (5)
6-h urine output between the IV and SC groups. Jugular venous distention* 12/16 (75) 17/19 (90) 29/35 (83)
STATISTICAL METHODS. The Shapiro-Wilk test was Rales/diminished breath sounds 5 (26) 12 (57) 17 (43)
used to determine data distribution. Parametric Lower extremity edema 16 (84) 18 (86) 34 (85)

continuous variables are given as mean
SD, and Dyspnea on exertion 18 (95) 21 (100) 39 (98)
Orthopnea/paroxysmal nocturnal 9 (47) 12 (57) 21 (53)
nonparametric continuous variables are reported as
dyspnea
medians and interquartile ranges. Comparisons were Fatigue 8 (42) 8 (38) 16 (40)
made using the Student t or Wilcoxon rank sum tests. Serum sodium, mmol/l 139 (137–142) 139 (137–140) 139 (137–142)
Categorical variables are presented as percentages Creatinine, mg/dl 1.2 (0.9–1.6) 1.3 (0.9–1.7) 1.3 (0.9–1.7)
and were compared using the chi-squared test. Glomerular filtration rate, 67
32 57
21 62
53
ml/min/1.73 m2†
The pre-specified threshold for significance was a
proBNP, pg/dl 1,556 (198–3,449) 1,545 (501–3,123) 1,551 (435–3,278)
p value <0.05. All statistical analyses were performed
using STATA version 13 software (Stata Corp., College Values are mean
SD, n (%), median (IQR), or n/N (%). *Presence or absence of jugular venous distention re-
ported in 16 and 19 subjects in the IV and SQ groups, respectively. †Calculated using the Modification of Diet in
Station, Texas). Renal Disease Study equation.
ACE ¼ angiotensin-converting enzyme; ARB ¼ angiotensin receptor blocker; IQR ¼ interquartile range;
RESULTS IV ¼ intravenous; proBNP ¼ pro–B-type natriuretic peptide; SQ ¼ subcutaneous.

Forty-one patients were enrolled in the study. One

patient was a screen failure after randomization and Baseline characteristics are described in Table 1.
prior to receiving study drug due to lack of need for IV Study subjects were average 57
13 years of age, 55%
diuretic on reassessment. Twenty-one patients were female; and the average body mass index was
received SC furosemide, and 19 patients received IV 38.7
11.2 kg/m 2. The mean home oral furosemide
furosemide. The mean IV dose administered was daily dose was 246
167 mg. No meaningful baseline
123
47 mg, with 58% of subjects receiving the clinical differences were observed between IV and SC
maximum dose of 160 mg. groups (Table 1).
68 Gilotra et al.
Subcutaneous Furosemide in Heart Failure
F I G U R E 1 Hourly Urine Output With Diuresis
Boxes show the median hourly urine output in intravenous (blue) and subcutaneous (red)
furosemide groups as shown by the line inside the box. Box limits depict the
interquartile range. *p < 0.05, using Wilcoxon rank sum test comparing intravenous with
subcutaneous furosemide.
After study drug administration, median 6-h
urine output in the IV group was not significantly
different than that in the SC group (IV: 1,425 ml; IQR:
1,075 to 1,950 ml vs. 1,350 ml in the SC group; IQR: 900
to 1,900 ml; p ¼ 0.84). Mean urine output in the IV
group also did not differ significantly from that in the
SC group (IV: 1,636 ml; 95% confidence interval [CI]:
1,182 to 2,089 ml vs. SC: 1,514 ml; 95% CI: 1,182 to 1,847
ml; mean difference between groups: 121 ml; 95%
CI: 415 to 658 ml; p ¼ 0.649). Maximum 6-h urine
output was 4,325 ml in the IV group and 3,200 ml in the
SC group. Hourly urine output was significantly lower
in the SC group at hour 2 (IV: 425 ml vs. SC: 250 ml;
p ¼ 0.02) and higher in the SC group at hour 6 (IV: 125 ml
vs. SC: 325 ml; p ¼ 0.005) (Figure 1).
Weight loss between the 2 groups was not signifi-
cantly different (IV: 1.5
1.1 kg vs. SC: 1.5
1.2 kg;
p ¼ 0.95). There was a trend toward increased
natriuresis, as measured by change in urinary
sodium concentration, in the SC group (IV: 7.3

35.3 mEq/l; vs. SC: 32.8
43.6 mEq/l; p ¼ 0.05).
Serum creatinine concentration decreased post-
diuresis to a similar extent in both groups
(IV: 0.07
0.14 mEq/l vs. SC: 0.05
0.16 mEq/dl;
p ¼ 0.70). Although the percent change in baseline
proBNP concentration decreased in the IV group
(2
14 mEq/l) and increased in the SC group
(þ3.5
13 mEq/l), the difference was not statistically
significant (p ¼ 0.21).
JACC: HEART FAILURE VOL. 6, NO. 1, 2018
JANUARY 2018:65–70
There were no events of worsening renal function,
severe electrolyte disturbances, arrhythmia, ototox-
icity, or skin irritation with either formulation. There
was 1 case of mild hypokalemia in the SC group, in
which the pre-diuresis serum potassium concentra-
tion of 4.1 mEq/l fell to 3.3 mEq/l.
At 1-, 7- and 30-day follow ups, no patients in the
SC group reported delayed skin irritation or pain at
infusion site after leaving the clinic. There was a
42% (n ¼ 8 of 19 subjects) 30-day hospitalization rate
in the IV group compared with a 52% (n ¼ 11 of 21
subjects) 30-day hospitalization rate in the SC group
(p ¼ 0.55). Within 7 days of study drug administra-
tion, 6 subjects in the IV group and 10 in the SC group
(p ¼ 0.35) required repeat IV diuretic administration
in the clinic or emergency department or were
admitted.
DISCUSSION
There have been limited advancements in diuretic
therapy in decompensated HF, despite diuretics
serving as the mainstay for relief of congestion for
several decades. This is the first study to examine the
efficacy of a novel SC formulation of the loop diuretic
furosemide administered by 5-h fixed-dose infusion
in patients presenting with worsening HF in the
outpatient setting. We found that the 80-mg 5-h
infusion of scFurosemide achieved diuresis and
weight change similar to and effectively as that of IV
furosemide at an average 50% higher dose, without
any differences in adverse events.
The biphasic diuretic administration regimen used
in this study was designed to achieve maximum
diuretic efficiency, that is, milliliters of urine output
per milligram of drug. We were initially concerned
that using only 80 mg of SC furosemide would be an
insufficient amount of furosemide as many of our
patients were receiving higher oral doses. The 80-mg
dose is a fixed dose determined by tolerability studies
of the volume of drug that can be infused and by
pharmacokinetic studies showing a sustained thera-
peutic drug level. Despite the fact that the IV group
received a greater average dose of furosemide, there
were no differences in urine output volume at 6 h.
Buckley et al. (7) administered a total IV bolus dose of
260 mg of furosemide followed by an infusion strat-
egy to a similar patient population and demonstrated
a median urine output of 1,045 ml over the course of a
clinic visit. Based on our current study, 80 mg SC
furosemide administered in this biphasic regimen is
clearly an efficacious dose for HF patients with acute
volume overload.
JACC: HEART FAILURE VOL. 6, NO. 1, 2018
JANUARY 2018:65–70
The efficacy of the lower SC dose is in part due to
its better bioavailability, in addition to the slow
infusion design. In a small study of healthy volun-
teers, low-dose SC furosemide (20 mg) produced both
diuretic (1,430
504 ml vs. 459
279 ml urine
output; p < 0.05) and natriuretic (134
31 mEq/l vs.
29
17 mEq/l urine sodium; p < 0.05) effects
compared with placebo (8). A study using a contin-
uous SC infusion by using an elastomeric pump for 4
to 5 days demonstrated a significant weight change
from baseline of 79.4 kg to 77.3 kg (10). Prior studies
of oral furosemide have demonstrated low bioavail-
ability (72%) with wide variability within individual
patients (11). Using the SC formulation studied and
administered at the same doses as in the current
study, scFurosemide has been shown to achieve
therapeutic plasma levels within 30 min of adminis-
tration as well as nearly 100% bioavailability (9).
In comparison, the mean bioavailability of the
oral formulation was 61% of the SC formulation.
Compared with both oral and IV formulations in
pharmacokinetic studies, the SC groups avoided peak
concentrations and demonstrated a constant rate of
absorption (9). In our study, subjects in the scFur-
osemide group had more robust hourly urine output
later in the 6-h observation window than that in the
IV group. This difference may reflect the more
consistent drug level attained by SC formulation than
that in the early peak seen with bolus IV administra-
tion. It is also possible that the SC group would have
had ongoing diuresis and greater total urine output
over a longer window of time (8 to 12 h), given the
later peak in urine output in the SC group seen in this
study. Additionally, despite the average body mass
index of 38.7
11.2 kg/m2 in our study subjects, the
SC group had an equally robust urinary and a greater
natriuretic response than that in the IV group. This
further emphasizes the efficacy of the SC route of
administration. Further study is needed to assess the
delayed (previous 6-h) effects of SC furosemide.
Prior formulations of SC furosemide have been
limited by the alkaline pH, allowing only low-volume
injection and causing frequent administration site
burning and stinging (8,12). Alternative strategies to
administration of the SC formulation have been the
use of an elastomeric pump; however, that too has
limitations as it requires catheter placement and
continuous infusion and has been complicated by
frequent site reactions including abscess formation
(10,12). In an attempt to address some of these hur-
dles to SC administration of furosemide, the scFur-
osemide used in this study was developed with a
physiologic pH of 7.4 and the ability to administer it
Gilotra et al. 69
Subcutaneous Furosemide in Heart Failure
through an infusion pump. Notably, there were no
skin administration site reactions or patient reports of
discomfort acutely or at follow-up. This new mode of
furosemide administration therefore seems to have
eliminated prior concerns of skin irritation and infu-
sion intolerability.
Acute HF is a burgeoning epidemic and accounts
for more than 1 million hospitalizations annually in
the United States (2). Additionally, 25% of patients
hospitalized with HF are readmitted within 30 days of
discharge (13). HF health care costs are expected to
approach $70 billion by 2030 (6). The main driver for
these HF presentations is congestion that necessi-
tates IV diuretic therapy in a hospital or clinic setting
with a certified health care professional. Therefore,
the potential use of SC rather than IV furosemide in
the management of volume overload has significant
clinical implications by shifting treatment outside the
hospital setting.
Already, SC medications are used in patients under
palliative or hospice care to avoid venous access and
improve patient comfort. Small retrospective case
series have demonstrated the efficacy of SC admin-
istration of furosemide in end-stage HF patients to
relieve dyspnea and congestion in home or hospice
settings (14–16). Our study expands the possibility of
applying this novel treatment strategy in patients
with less advanced HF presenting to the outpatient
clinic with an acute decompensation, who can be
treated and discharged home without an admission.
Ultimately, the goal would be to send patients home
with SC furosemide or to prescribe the medication
without the patient having to come in to the clinic or
hospital. The current need for patients to present to a
clinical setting naturally delays diuretic administra-
tion, and it has recently been demonstrated that
earlier administration of diuretics in the emergency
department is associated with improved outcomes in
cases of worsening HF (17). The furosemide formula-
tion in this study is being developed to be adminis-
tered through a wearable SC drug delivery infusor
(i.e., a patch pump) for use outside the acute care
setting. This strategy’s safety and impact on use of
resources warrants future investigation.
STUDY LIMITATIONS. This was a small, single-center
study carried out at an urban tertiary care center, thus
potentially limiting generalizability. However, it is
the largest study of its nature, assessing the SC
administration of furosemide in patients with ADHF,
and the first study to evaluate a novel, pH-neutral
formulation of furosemide in patients with volume
overload presenting to an outpatient HF clinic.
Additionally, this was a high-risk outpatient HF
70 Gilotra et al. JACC: HEART FAILURE VOL. 6, NO. 1, 2018

Subcutaneous Furosemide in Heart Failure JANUARY 2018:65–70

cohort, in which nearly one-half the patients required for the outpatient management of HF. Future inves-
hospitalization during study follow-up. This likely tigation is required to assess home self-
speaks to the population treated in the HFBC but also administration of scFurosemide and its potential
to study design, which required subjects to remain in effects on HF hospitalization reduction.
clinic for 6 h, thus limiting participant enrollment
ACKNOWLEDGMENT The authors thank Kenneth
perhaps to those patients who are seen frequently for
Shermock, PharmD, PhD (Johns Hopkins School of
IV diuresis and are, therefore, at higher risk for future
Public Health) for reviewing the manuscript.
diuresis need or hospitalization. Although the longer
administration time of the SC formulation may be
ADDRESS FOR CORRESPONDENCE: Dr. Nisha A.
seen as a barrier to widespread use, the benefit of 5-h
Gilotra, Division of Cardiology, Department of Medi-
administration is the maximization of diuretic effi-
cine, Johns Hopkins School of Medicine, 600 North
ciency, which allows a more steady-state concentra-
Wolfe Street, Carnegie Building, Suite 568c, Balti-
tion and prolonged diuresis, as we demonstrate.
more, Maryland 21287. E-mail: naggarw2@jhmi.edu.
CONCLUSIONS

PERSPECTIVES
This study, the first in outpatients with worsening
HF, demonstrated clinical efficacy and safety of SC
COMPETENCY IN MEDICAL KNOWLEDGE:
administration of furosemide that was comparable to
In patients with worsening HF, fixed-dose SC
that of IV furosemide. We describe the first clinical
administration of scFurosemide resulted in diuresis
comparison between the fixed dose of a novel, pH-
that was similar to bolus dose IV furosemide.
neutral formulation of furosemide and our standard
regimen, which involved IV administration of a dose
TRANSLATIONAL OUTLOOK: Future studies are
that was approximately 50% higher. The findings of
needed to assess the use of scFurosemide at home
this study corroborate the design premise that a
and the impact of such an intervention on outcomes in
higher diuretic efficiency can be achieved by slower
patients with HF.
infusion compared to that of the IV bolus. Addition-
ally, these results have significant implications

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